153907-80-3Relevant academic research and scientific papers
Synthesis, biological evaluation, and molecular modeling of nitrile-containing compounds: Exploring multiple activities as anti-Alzheimer agents
Silva, Daniel,Mendes, Eduarda,Summers, Eleanor J.,Neca, Ana,Jacinto, Ana C.,Reis, Telma,Agostinho, Paula,Bolea, Irene,Jimeno, M. Luisa,Mateus, M. Luisa,Oliveira-Campos, Ana M. F.,Unzeta, Mercedes,Marco-Contelles, José,Majekova, Magdalena,Ramsay, Rona R.,Carreiras, M. Carmo
, p. 215 - 231 (2019/09/03)
Based on the monoamine oxidase (MAO) inhibition properties of aminoheterocycles with a carbonitrile group we have carried out a systematic exploration to discover new classes of carbonitriles endowed with dual MAO and AChE inhibitory activities, and Aβ anti-aggregating properties. Eighty-three nitrile-containing compounds, 13 of which are new, were synthesized and evaluated. in vitro screening revealed that 31, a new compound, presented the best lead for trifunctional inhibition against MAO A (0.34 μM), MAO B (0.26 μM), and AChE (52 μM), while 32 exhibited a lead for selective MAO A (0.12 μM) inhibition coupled to AChE (48 μM) inhibition. Computational analysis revealed that the malononitrile group can find an advantageous position with the aromatic cleft and FAD of MAO A or MAO B. However, the total binding energy can be handicapped by an internal penalty caused by twisting of the ligand molecule and subsequent disruption of the conjugation (32 in MAO B compared to the conjugated 31). Conjugation is also important for AChE as well as the hydrophilic character of malononitrile that allows this group to be in close contact with the aqueous environment as seen for 83. Although the effect of 31 and 32 against Aβ1–42, was very weak, the effect of 63 and 65, and of the new compound 75, indicated that these compounds were able to disaggregate Aβ1–42 fibrils. The most effective was 63, a (phenylhydrazinylidene)propanedinitrile derivative that also inhibited MAO A (1.65 μM), making it a potential lead for Alzheimer's disease application.
Electrochemically initiated tandem and sequential conjugate addition processes: One-pot synthesis of diverse functionalized isoindolinones
Antico, Pasqualmorica,Capaccio, Vito,Di Mola, Antonia,Massa, Antonio,Palombi, Laura
supporting information; experimental part, p. 1717 - 1724 (2012/07/28)
A tandem aldol-heterocyclization-rearrangement reaction and one-pot sequential Michael addition allowed a direct access to highly functionalized 3-isoindolinones containing quaternary carbon centers. The desired products are obtained under mild conditions and in short reaction times by galvanostatic electrolysis in a divided cell. A further tandem intramolecular heterocyclization reaction leading to synthetically relevant hemiaminal derivatives has been established with suitable Michael acceptors. Copyright
Structure-based design of pyridopyrimidinediones as dipeptidyl peptidase IV inhibitors
Lam, Betty,Skene, Robert J.,Zhang, Zhiyuan,Stafford, Jeffery A.,Shi, Lihong,Gwaltney II, Stephen L.
, p. 6628 - 6631,4 (2012/12/12)
Dipeptidyl peptidase IV (DPP-4) inhibitors have been shown to enhance GLP-1 levels and thereby improve hyperglycemia in type II diabetes. From a small fragment hit, using structure-based design, we have discovered a new class of non-covalent, potent and s
On the reaction of o-functional benzylmalononitriles with N-bisnucleophiles as well as alcoholates
Troschutz,Grun
, p. 865 - 869 (2007/10/02)
The o-functional benzylmalononitriles 1, 16 and 22 show different reactivity towards N-bisnucleophiles and alcoholates. 16 and 22 cyclize with guanidine to the pyrimidinetriamines 17 and 23 only while compound 1 provides 4 by a twofold ring closure. 1 reacts with hydrazine and ethylendiamine to afford the 2-benzazepines 7 and 12, respectively. Refluxing compound 22 with Na-methylate or Na-ethylate, respectively, leads to the 2-benzazepine-cyanoenolether 26a,b. Analogous reactions with 16 did not succeed in cyclization.
